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Chapter 8
Genome Evolution
Jocelyn E. Krebs
Figure 08.CO: A circular genome map showing shared regions between humans (outer
ring) and (from inner ring outwards) chimpanzee, mouse, rat, dog, chicken, and
zebrafish genomes.
© Martin Krzywinski/Photo Researchers, Inc.
8.1 Introduction
Comparative genomics
8.2 DNA Sequences Evolve by Mutation and a
Sorting Mechanism
• The probability of a mutation is influenced by the likelihood
that the particular error will occur and the likelihood that it
will be repaired (homologous and site-specific recombination).
• Transversion and transition mutation
• Transversion is less common and easily detected by repair
system
•
synonymous mutation – A change in DNA sequence in a coding region that
does not alter the amino acid sequence of the polypeptide product.
•
 silent muation
•
nonsynonymous mutation –A change in DNA sequence in a coding region that
alters the amino acid sequence of the polypeptide product.
•
 missense or nonsense mutation
•
Neutral mutation- no phenotype chance, noncoding region mutation
Genetic drift
In small populations, the frequency of a
mutation will change randomly and new
mutations are likely to be eliminated by chance
fixation –The process by which a new allele
replaces the allele that was previously
predominant in a population.
Figure 08.01 The fixation or loss of
alleles by random genetic drift
Data courtesy of Kent E. Holsinger, University of
Connecticut [http://darwin.eeb.uconn.edu]
• The frequency of a neutral mutation largely depends on
genetic drift, the strength of which depends on the size of the
population.
• The frequency of a mutation that affects phenotype will be
influenced by negative or positive selection.
Data courtesy of Kent E. Holsinger, University of
Connecticut [http://darwin.eeb.uconn.edu]
8.3 Selection Can Be Detected by Measuring
Sequence Variation
• The ratio of nonsynonymous to synonymous substitutions in
the evolutionary history of a gene is a measure of positive or
negative selection.
• Ks/Ka< 1: negative selection common event
• Ks/Ka>1 positive selection
• Example 1) antigenic proteins of some pathogens
2) sexual selection; traits
3) MHC (2-10)
•
•
Low heterozygosity of a gene may indicate recent selective events.
genetic hitchhiking – The change in frequency of a genetic variant due to its
linkage to a selected variant at another locus.
Figure 08.02: Nonsynonymous and synonymous variation in the Adh locus in
Drosophila melanogaster (“polymorphic”) and between D. melanogaster, D. simulans,
and D. yakuba (“fixed”).
Adapted from J. H. McDonald, J. H. and M. Kreitman,
Nature 351 (1991): 652-654.
• Comparing the rates of substitution among related species
can indicate whether selection on the gene has occurred.
Figure 08.03: A higher number of nonsynonymous substitutions in lysozyme
sequences in the cow/deer lineage as compared to the pig lineage.
Adapted from N. H. Barton, et al. Evolution. Cold Spring Harbor
Laboratory Press, 2007. Original figure appeared in J. H. Gillespie,
The Causes of Molecular Evolution. Oxford University Press, 1991.
Figure 08.04: Nucleotide diversity (pi) of the tb1 region in domesticated maize is much
lower than in wild teosinte, indicating strong selection on this locus in maize.
Reproduced from R. M. Clark, et al., Proc. Natl. Acad. Sci. USA 101
(2004): 700-707. Copyright © 2004 National Academy of Sciences,
U.S.A. Courtesy of John F. Doebley, University of Wisconsin, Madison
linkage disequilibrium – A nonrandom association between alleles at two
different loci, often as a result of linkage.
Figure 08.05: The fraction of recombinants between an allele of G6PD and alleles at
nearby loci on a human chromosome remains low.
Adapted from E. T. Wang, et al., Proc. Natl. Acad. Sci. USA
103 (2006): 135-140.
8.4 A Constant Rate of Sequence Divergence Is a
Molecular Clock
• The sequences of orthologous genes in different species vary
at nonsynonymous sites (where mutations have caused amino
acid substitutions) and synonymous sites (where mutation has
not affected the amino acid sequence).
• Synonymous substitutions accumulate ~10× faster than
nonsynonymous substitutions.
• Divergence
• Codon bias-A higher usage of one codon in genes to encode
amino acids for which there are several synonymous codons.
Molecular clock
Figure 08.06: The rate of evolution of three types of proteins over time. The
approximately constant rate of evolution of each protein type is a molecular clock.
Reproduced with kind permission from Springer Science+Business
Media: J. Mol. Evol., The structure of cytochrome and the rates of
molecular evolution, vol. 1, 1971, pp. 26-45, R. E. Dickerson, fig. 3.
Courtesy of Richard Dickerson, University of California, Los Angeles.
Nonsynonymous substitution (AA change) is deleterious. Thus it is eliminated by natural selection
Advantageous few mutation can be accumulated fixation
Random genetic drift-Fixation
Divergence
Replacement site vs silent site
Condon bias
Comparison between d and b chain; 10 differences in 146 residue divergence=6.9%
31 base pair/441 bp 11 in 330 replacement (3.7%) vs 20 in 111 silent (32%)
Theoratically, 105 mutation in nonsynonymous region.
• The evolutionary divergence
between two DNA sequences is
measured by the corrected
percent of positions at which the
corresponding nucleotides differ.
• Substitutions may accumulate at
a more or less constant rate
after genes separate, so that the
divergence between any pair of
globin sequences is proportional
to the time since they shared
common ancestry.
Figure 08.07: Divergence of DNA sequences depends on evolutionary separation. Each
point on the graph represents a pairwise comparison.
0.12%/million years- nonsynonymous divergence
Duplication 0.1%/million years
(50% nonsynonymous divergence)
 500 million years
Figure 08.08: All globin genes have evolved by a series of duplications, transpositions,
and mutations from a single ancestral gene.
Figure 08.09: This tree accounts for the separation of classes of globin genes.
Figure 08.10: An ancestral consensus sequence for a family is calculated by taking the
most common base at each position.
8.5 The Rate of Neutral Substitution Can Be
Measured from Divergence of Repeated
Sequences
• The rate of substitution per year at neutral sites is greater in
the mouse genome than in the human genome, probably
because of a higher mutation rate.
2.2X10-9 vs 4.5X10-9
Figure 08.10: An ancestral consensus sequence for a family is calculated by taking the
most common base at each position.
8.6 How Did Interrupted Genes Evolve?
• A major evolutionary question is whether genes originated
with introns or whether they were originally uninterrupted.
• “introns late” model – The hypothesis that the earliest genes
did not contain introns, and that introns were subsequently
added to some genes.
• Interrupted genes that correspond either to proteins or to
independently functioning nonprotein-encoding RNAs
probably originated in an interrupted form (the “introns
early” hypothesis).
exon shuffling – The
hypothesis that genes have
evolved by the
recombination of various
exons encoding functional
protein domains.
A special class of introns is
mobile and can insert
themselves into genes.
Figure 08.11: An exon surrounded by flanking sequences that is translocated into an
intron may be spliced into the RNA product.
8.7 Why Are Some Genomes So Large?
Figure 08.12: DNA content of the
haploid genome increases with
morphological complexity of lower
eukaryotes, but varies extensively
within some groups of higher
eukaryotes.
• There is no clear correlation
between genome size and genetic
complexity.
• C-value – The total amount of DNA
in the genome (per haploid set of
chromosomes).
• C-value paradox – The lack of
relationship between the DNA
content (C-value) of an organism
and its coding potential.
8.7 Why Are Some Genomes So Large?
• There is an increase in the minimum genome size associated
with organisms of increasing complexity.
• There are wide variations in the genome sizes of organisms
within many taxonomic groups.
Figure 08.13: The minimum genome size found in
each taxon increases from prokaryotes to mammals.
8.8 Morphological Complexity Evolves by
Adding New Gene Functions
Figure 08.15: Human genes can be
classified according to how widely
their homologues are distributed in
other species.
• In general, comparisons of
eukaryotes to prokaryotes,
multicellular to unicellular
eukaryotes, and vertebrate animals
to invertebrate animals show a
positive correlation between gene
number and morphological
complexity as additional genes are
needed with generally increased
complexity.
8.8 Morphological Complexity Evolves by
Adding New Gene Functions
Figure 08.16: Common eukaryotic
proteins are concerned with essential
cellular functions.
Figure 08.17: Increasing complexity in
eukaryotes is accompanied by accumulation
of new proteins for transmembrane and
extracellular functions.
8.9 Gene Duplication Contributes to Genome
Evolution
• Most of the genes that are
unique to vertebrates are
concerned with the immune or
nervous systems.
• Duplicated genes may diverge
to generate different genes, or
one copy may become an
inactive pseudogene.
Figure 08.18: After a globin gene has
been duplicated, differences may
accumulate between the copies. The
genes may acquire different functions or
one of the copies may become inactive.
Fate of duplicated genes
1.Working as intact genes; different time,
different cell type
2.Inactivated pseudogene
8.10 Globin Clusters Arise by Duplication and
Divergence
Figure 08.19: Each of the alphalike and beta-like globin gene
families is organized into a single
cluster that includes functional
genes and pseudogenes (psi).
• All globin genes are descended by
duplication and mutation from an
ancestral gene that had three exons.
• The ancestral gene gave rise to
myoglobin, leghemoglobin, and α and b
globins.
• The α- and b-globin genes separated in
the period of early vertebrate evolution,
after which duplications generated the
individual clusters of separate α- and blike genes.
8.10 Globin Clusters Arise by Duplication and
Divergence
• nonallelic genes – Two (or more) copies of the same gene
that are present at different locations in the genome
(contrasted with alleles, which are copies of the same gene
derived from different parents and present at the same
location on the homologous chromosomes).
• Once a gene has been inactivated by mutation, it may
accumulate further mutations and become a pseudogene (),
which is homologous to the active gene(s) but has no
functional role.
Figure 08.20: Different hemoglobin genes are expressed during embryonic, fetal, and
adult periods of human development.
Figure 08.21: Clusters of -globin genes and pseudogenes are found in vertebrates.
8.11 Pseudogenes Are Nonfunctional Gene
Copies
Figure 08.22: Many changes have
occurred in a -globin gene since it
became a pseudogene.
• Processed pseudogenes result
from reverse transcription and
integration of mRNA transcripts.
• Nonprocessed pseudogenes result
from incomplete duplication or
second-copy mutation of functional
genes.
• Some pseudogenes may gain
functions different from those of
their parent genes, such as
regulation of gene expression, and
take on different names.
Figure 08.23: Most human RP pseudogenes are of recent origin; many are shared with
the chimpanzee but absent from rodents.
Adapted from S. Balasubramanian, et al., Genome Biol. 20 (2009): R2.
8.12 Genome Duplication Has Played a Role in
Plant and Vertebrate Evolution
• Genome duplication occurs when polyploidization increases
the chromosome number by a multiple of two.
• autopolyploidy – Polyploidization resulting from mitotic or
meiotic errors within a species.
• allopolyploidy – Polyploidization resulting from hybridization
between two different but reproductively compatible species.
8.12 Genome Duplication Has Played a Role in
Plant and Vertebrate Evolution
• Genome duplication events can be obscured by the evolution
and/or loss of duplicates as well as by chromosome
rearrangements.
• Genome duplication has been detected in the evolutionary
history of many flowering plants and of vertebrate animals.
• 2R hypothesis – The hypothesis that the early vertebrate
genome underwent two rounds of duplication.
Figure 08.24: Genomnic Duplication
Adapted from G. Blanc and K. H. Wolfe, Plant Cell 16 (2004):
1667-1678.
8.13 What Is The Role of Transposable Elements
in Genome Evolution?
• Transposable elements tend to increase in copy number when
introduced to a genome but are kept in check by negative
selection and transposition regulation mechanisms.
8.14 There May Be Biases in Mutation, Gene
Conversion, and Codon Usage
• Mutational bias may account for a high AT content in
organismal genomes.
• Gene conversion bias, which tends to increase GC content,
may act in partial opposition the mutational bias.
• Codon bias may be a result of adaptive mechanisms that favor
particular sequences, and of gene conversion bias.
Figure 08.24: Genomnic Duplication
Adapted from G. Blanc and K. H. Wolfe, Plant Cell 16 (2004): 1667-1678.